Abstract #45

Hcm1 is an S phase-specific hub in the transcriptional circuitry of the cell cycle that is required for high fidelity chromosome transmission. Tata Pramila¹, Wei Wu^{1, 2}, Shawna Miles¹, William Stafford Noble², Linda Breeden¹. 1) Basic Sci Division, Fred Hutchinson Cancer Res Ctr, Seattle, WA; 2) Dept. Genome sciences, University of Washington, Seattle, WA.
   Using new microarray data through the cell cycle, we have identified hundreds of new periodic transcripts of budding yeast. For each periodic transcript we have calculated a peak time as a weighted average from the analysis of five cell cycle data sets. These data can be displayed, filtered and sorted within an interactive web site. We have used these peak times to identify coordinately regulated genes and their regulators. We have searched for phylogenetically conserved and over-represented motifs in the promoters of genes whose transcripts peak in S phase. One such sequence, AYAAACAA, is related to the binding site for Hcm1 characterized in vitro by Zhu and Davis (BBA 1448,236) who picked up Hcm1 as a high copy suppressor of a spindle pole defect. Hcm1 is a transcription factor in the fork head family. We have used the isolated element identified in our search in reporter constructs to show that it is an activator of transcription that is Hcm1-dependent. We find this sequence to be conserved across species in 180 cell cycle regulated transcripts, most of which peak in S phase. These putative targets of Hcm1 show a highly significant enrichment for genes involved in spindle pole body and kinetochore formation. Hcm1 is an unstable protein and its expression peaks in late G1. Hcm1 overproduction is deleterious and hcm1 mutants display chromosome transmission defects. Eight Hcm1 targets have been confirmed by transcript analysis. These targets also include other cell cycle-specific transcription factors, which position Hcm1 as a key S phase regulator in the transcriptional circuitry of the cell cycle.

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